Chemokine

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Chemokine

Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8—10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. These proteins have historically been known under several other names including the SIS family of cytokines , SIG family of cytokines , SCY family of cytokines , Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro- inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection , while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates , some viruses and some bacteria , but none have been found in other invertebrates. All of these proteins exert their biological effects by interacting with G protein -linked transmembrane receptors called chemokine receptors , that are selectively found on the surfaces of their target cells. The major role of chemokines is to act as a chemoattractant to guide the migration of cells. Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine. Some chemokines control cells of the immune system during processes of immune surveillance, such as directing lymphocytes to the lymph nodes so they can screen for invasion of pathogens by interacting with antigen-presenting cells residing in these tissues. These are known as homeostatic chemokines and are produced and secreted without any need to stimulate their source cells. Some chemokines have roles in development; they promote angiogenesis the growth of new blood vessels , or guide cells to tissues that provide specific signals critical for cellular maturation. Other chemokines are inflammatory and are released from a wide variety of cells in response to bacterial infection, viruses and agents that cause physical damage such as silica or the urate crystals that occur in gout. Their release is often stimulated by pro-inflammatory cytokines such as interleukin 1.

However, chemokine, anti-human-receptor antibodies can be used in severe combined immunodeficiency SCID mice, as was shown by chemokine abrogation of breast cancer metastasis to the lung in mice injected with a human breast carcinoma cell line, thereby confirming the role of CXCR4 in metastasis Auten, chemokine, R.

The chemokines or chemotactic cytokines are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells leukocytes. Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post-translational modification, by interaction with the extracellular matrix ECM , and by binding to heptahelical 'atypical' chemokine receptors that regulate chemokine localization and abundance.

The chemokines or chemotactic cytokines are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells leukocytes. Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post-translational modification, by interaction with the extracellular matrix ECM , and by binding to heptahelical 'atypical' chemokine receptors that regulate chemokine localization and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarizes the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focusing particularly on their ability to direct leukocyte migration. Keywords: atypical chemokine receptor; cell migration; chemokine; chemokine receptor; glycosaminoglycan; immune surveillance; inflammation; leukocyte; oligomerization; protease. Abstract The chemokines or chemotactic cytokines are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. Publication types Research Support, Non-U.

Chemokine

Cytokine proteins are classified as chemokines according to behavior and structural characteristics. In addition to being known for mediating chemotaxis, chemokines are all approximately 8—10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. These proteins have historically been known under several other names including the SIS family of cytokines , SIG family of cytokines , SCY family of cytokines , Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro- inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection , while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates , some viruses and some bacteria , but none have been found in other invertebrates. All of these proteins exert their biological effects by interacting with G protein -linked transmembrane receptors called chemokine receptors , that are selectively found on the surfaces of their target cells. The major role of chemokines is to act as a chemoattractant to guide the migration of cells. Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine.

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Many modified chemokines have been described as antagonists in vitro on the basis of several studies involving N-terminal truncation to produce receptor antagonists of the CXCL8 and CCL2 receptors 8 , 9 , 63 , 64 , Because both these receptors are expressed on eosinophils, this selectivity could be advantageous for the development of an anti-asthma therapy. Chemokine receptor inhibitors in cancer. Cancer and the chemokine network. Kostrikis, L. Interfering with an essential link in the chain CCR1 or CXCR3 in the case of organ allograft transplant might therefore result in a total inhibition of the inflammatory process. This understandably led to the development of small molecule cCKR antagonists to trial in patients with immune or inflammatory disease In renal cell carcinoma, ACKR3 expressed by endothelial progenitor cells and tumoral ECs exerts a proangiogenic role inducing their migration and survival Lancet Oncol. Cancer-related inflammation, common themes and therapeutic opportunities. Figure 4. EMBO J 34 , —

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Genes Immun. An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition. Lancet Oncol. Copy Download. Nature Reviews. The lymphatic system controls intestinal inflammation and inflammation-associated Colon Cancer through the chemokine decoy receptor D6. Bitsch, A. One of the main hurdles encountered in the development of small molecule receptor antagonists is the loss of species crossreactivity as the affinity for the human receptor increases, which creates problems for testing in animal models, as was found with BX Ref. Given that chemokines and their receptors have been found involved in several aspects of cancer biology, their possible targeting was evaluated in many preclinical studies and clinical trials Table 1 and Figure 1. Cancer Immunol Res. Their homeostatic function in homing is best exemplified by the chemokines CCL19 and CCL21 expressed within lymph nodes and on lymphatic endothelial cells and their receptor CCR7 expressed on cells destined for homing in cells to these organs. Nat Immunol 16 , — Nomenclature for chemokine receptors.